Neuroprotective effects of atomoxetine against traumatic spinal cord injury in rats

Spinal cord injury (SCI) often causes serious and irreversible neurological deficit leading to disability or impairment of normal physical activity. Atomoxetine, a selective norepinephrine transporter (NET) inhibitor has gained much attention in the field of the neurodevelopmental disorder, but its effect on SCI has not been evaluated. The present study has been undertaken to investigate the neuroprotective effects of atomoxetine.

Administration of atomoxetine 20 mg/kg IP was compared with methylprednisolone (MP) 30 mg/kg IP in traumatic spinal cord injured Wistar rats. Tissue samples were evaluated for apoptosis, inflammation, and oxidative stress, along with histopathological examination and neurological evaluation.

There was no significant difference in the caspase-3 activity between the control and the sham groups or between the MP and the atomoxetine groups (P=0.811). The administration of atomoxetine significantly reduced tissue tumour necrosis factor alpha (TNF-α), and nitric oxide (NO) levels compared to the trauma group (P<0.001). Treatment with atomoxetine also decreased the tissue myeloperoxidase (MPO) activity (P=0.026) and increased the tissue superoxide dismutase (SOD) activity compared to the trauma group (P=0.001 and P=0.004, respectively). Histopathological examination showed less degenerated neurons in the atomoxetine group compared to trauma group.

This is the first experimental evidence showing meaningful neuroprotective effects of atomoxetine over SCI through anti-apoptotic, anti-inflammatory, and antioxidant effects by reducing lipid peroxidation, which was confirmed by biochemical, histopathological and the functional evaluation.